NSTK · 01.2026Independent supplement reference
NutriStack
Edition 1.0Reviewed May 26, 2026

Protocol·Sleep·Beginner·Reviewed June 9, 2026

Restless Legs Relief Protocol.

A supportive, evidence-informed stack for restless legs syndrome that prioritizes correcting low iron stores (the most common reversible driver) alongside neuromuscular and B-vitamin support. Supplements are adjunctive only: test ferritin first and see a clinician for severe or worsening symptoms.

In short

The restless legs relief protocol in brief.

A quick summary. The full stack, with dose and timing for each supplement, is below.

The Restless Legs Relief Protocol is a beginner stack of 5 supplements aimed at sleep: Iron Bisglycinate, Magnesium Glycinate, Methylfolate, Methylcobalamin, and Vitamin D3. 2 are core and the rest are optional add-ons, at roughly $25-45/mo. Each supplement below lists its dose, timing, role, and the evidence behind it.

The stack

What is in the restless legs relief protocol.

Dose, timing, role, and evidence tier for each supplement. Core items carry the protocol; optional ones are situational. Open any name for the full profile.

SupplementDoseTimingRoleEvidence
Iron Bisglycinate25-50 mg elemental iron, only if ferritin is low (commonly below 75 ng/mL)Once daily or every other day on an empty stomach, away from coffee, tea, and calciumCoreStrong
Magnesium Glycinate200-350 mg elemental magnesiumEvening, about 1 hour before bedCoreEmerging
Methylfolate400-800 mcgMorning with foodOptionalEmerging
Methylcobalamin500-1000 mcgMorning with foodOptionalEmerging
Vitamin D31000-2000 IUMorning with the largest mealOptionalEmerging
Iron Bisglycinate

Low brain iron is the most consistent reversible factor associated with restless legs, and oral iron repletion can ease symptoms when iron stores are low. Take this only after a ferritin test confirms low stores, because iron overload is harmful.

Magnesium Glycinate

Magnesium supports normal nerve and muscle function and is often used for nighttime leg discomfort and cramping. Evidence for restless legs specifically is limited and mixed, so this is a low-risk adjunct rather than a proven treatment.

Methylfolate

Folate deficiency is a recognized secondary contributor to restless legs, particularly in pregnancy, so correcting a low or marginal folate status may help. Routine use without a documented deficiency is not established.

Methylcobalamin

Vitamin B12 is required for healthy peripheral nerve function, and low B12 can cause sensory leg symptoms that may mimic or worsen restless legs. Benefit is most plausible when B12 status is low or borderline rather than normal.

Vitamin D3

Observational studies link low vitamin D to greater restless legs severity, and small trials suggest that repletion in deficient people may reduce symptoms. This is supportive only and is best guided by a 25-hydroxyvitamin D level.

Why it works together

How the pieces combine.

The mechanistic rationale for stacking these together rather than taking them in isolation.

  • Restless legs is strongly linked to low ferritin: test ferritin first and take Iron Bisglycinate only if it is low, since iron overload is harmful. Severe, worsening, or refractory symptoms warrant evaluation by a clinician.
  • Iron Bisglycinate is the foundation of this stack. Take it apart from Magnesium Glycinate (separate by about 2 hours) because magnesium and other minerals can blunt iron absorption.
  • Take Iron Bisglycinate on an empty stomach and away from coffee, tea, and calcium-rich foods or supplements, which all reduce iron uptake. Pairing iron with a vitamin C source can improve absorption.
  • Methylfolate and Methylcobalamin work together in one-carbon metabolism and nerve maintenance, so taking them together in the morning is sensible. Do not start higher-dose folate without also confirming B12 status, since folate can mask a B12 deficiency.
  • Magnesium Glycinate is dosed in the evening for nighttime leg comfort and sleep onset, while Iron Bisglycinate and the B vitamins sit in the morning, which spaces the minerals apart and aligns each nutrient with its purpose.
  • Keep total supplemental magnesium within standard upper-limit guidance, and re-test ferritin periodically while supplementing iron so that stores do not climb too high. Stop iron and consult a clinician if ferritin normalizes or symptoms persist.
At a glance

Cost and commitment.

A rough monthly cost and how involved the protocol is to run.

Estimated cost
$25-45/mo
Difficulty
Beginner
Supplements
5 (2 core)
Sources

The evidence behind it.

Overview citations for this protocol. Each supplement's own profile carries its full source list.

  1. Allen RP et al. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria--history, rationale, description, and significance. Sleep Med. 2014;15(8):860-73. PubMed
  2. Trotti LM et al. Iron for the treatment of restless legs syndrome. Cochrane Database Syst Rev. 2019;1(1):CD007834. PubMed
  3. Garcia-Borreguero D et al. Guidelines for the first-line treatment of restless legs syndrome/Willis-Ekbom disease, prevention and treatment of dopaminergic augmentation: a combined task force of the IRLSSG, EURLSSG, and the RLS-foundation. Sleep Med. 2016;21:1-11. PubMed
FAQ

Common questions.

Quick answers drawn from the stack above.

What is in the Restless Legs Relief Protocol?

The Restless Legs Relief Protocol combines 5 supplements for sleep: Iron Bisglycinate, Magnesium Glycinate, Methylfolate, Methylcobalamin, and Vitamin D3. 2 are core; the rest are optional.

How much does the Restless Legs Relief Protocol cost?

NutriStack estimates the Restless Legs Relief Protocol at about $25-45/mo, depending on the forms and brands you choose and whether you run the optional add-ons.

Is the Restless Legs Relief Protocol backed by evidence?

Each supplement in the protocol carries its own evidence tier (1 rated strong here) and links to PubMed-cited sources. NutriStack does not rank or score brands and takes no manufacturer payments; this is an informational reference, not medical advice.

Build it in the app

Run the restless legs relief protocol in NutriStack.

Add the stack to NutriStack to track timing, screen it for interactions, and see a Stack Score that updates as you tune it.

NutriStack is an informational and organizational tool, not a medical service, and not a substitute for professional advice. Always consult a qualified healthcare professional before starting, stopping, or changing any supplement or medication.